Time for the next in our "Best of the Month" series.. At the time of it's original publication, Dr. Craig Horbinski had this to say about a study which had recently been published in Brain Pathology: "Only catch is whether the method is TOO sensitive. After all, if all
oligos are positive for IDH1, why do the "inferior" IDH tests
effectively stratify prognosis? I'll be keen to see if anyone else can replicate this work."
Here's the original post from October 22, 2012:
Although direct sequencing of mutations in isocitrate dehydrogenase 1 (IDH1) has been considered to be the gold
standard method to detect this mutation, the sensitivity of this
technique has been questioned especially because specimens from glial
tumors may contain large numbers of non-tumor cells. The group screened 141
cases of oligodendroglial tumors for IDH1 mutations using
peptide nucleic acid (PNA)-mediated clamping PCR and compared the
results with the results of direct sequencing, pyrosequencing, and
immunohistochemistry (IHC). Nested PCR was only performed in cases
having mutant IDH1 only discovered by clamping PCR. Using dilution experiments mixing IDH1
wild-type and mutant DNA samples, clamping PCR detected mutations in
samples with a 1% tumor DNA composition. Using PNA clamping PCR, the group
detected 138 of 141 (97.9%) cases with mutant IDH1 in the
series, which is significantly higher (P = 0.016; PNA clamping vs.
direct sequencing) than those of direct sequencing (74.5%),
pyrosequencing (75.2%), and IHC (75.9%). From these results, it appears that almost all
oligodendroglial tumors have IDH1 mutations, suggesting that IDH1 mutation is an early and common event especially in the development of oligodendroglial tumors.
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1 comment:
Interesting. Just had an IDH-1+ oligo.
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